attr-cardiomyopathy stabilization following tafamidis therapy

Conditions: Transthyretin Amyloidosis

Summary: the study will investigate the stabilization effects of tafamidis utilizing cardiac imaging cardiac magnetic resonance imaging (cmr). the investigators propose to pursue the following specific aims: 1. utilize cardiac magnetic resonance to assess stabilization of attr after tafamidis therapy based on extracellular volume mapping. 2. investigate left ventricular myocardial mass, native t1, t2, and extracellular volume mapping after 12 month follow-up. 3. utilize cardiac magnetic resonance feature tracking at baseline and at 12 month follow-up.

the investigators hypothesize that participants with earlier stages (nyha class i and class ii) of attr wild type and attr mutant will demonstrate stabilization of attr following 1 year of tafamidis. the investigators propose to pursue the following specific aims: 1. utilize cardiac magnetic resonance to assess stabilization of attr after tafamidis therapy based on extracellular volume mapping. 2. investigate left ventricular myocardial mass, native t1, t2, and extracellular volume mapping after 12 month follow-up. 3. utilize cardiac magnetic resonance feature tracking at baseline and at 12 month follow-up. the investigators will enroll 131 participants with confirmed attr. participants will be screened to exclude light chain amyloidosis by either measuring the proportion of kappa: lambda light chains with the serum free light chain assay, and tested for immunofixation electrophoresis of serum and urine. once participants has confirmed diagnosis of attr (pyrophosphate scan positive scoring \>1.5 ratio) and undergone baseline testing participants will be ask to enroll in the study. genetic testing will performed to further distinguish between mutation and wild type. all participants will be required to sign informed consent agreeing to follow up testing at 1 year. participants will undergo a baseline cardiac magnetic resonance imaging for the purpose of evaluating native t1, t2, first pass perfusion, and extracellular volumes for patients with glomerular filtration rate \>30. patients with glomerular filtration rate \<30 will only have native t1 and t2 values evaluated. if participants undergo implanted cardiac device during tafamidis therapy, follow up cardiac magnetic resonance imaging will only evaluate featuring tracking and left ventricular mass. left ventricular mass and cardiac magnetic feature tracking values will be extracted from all cardiac magnetic resonance imaging studies. after one year of tafamidis therapy, participants will return to initial facility where testing was preformed to undergo a follow up cardiac magnetic resonance imaging study. there is emerging evidence that there may be biomarkers yet identified for earlier detection of this disease. henceforth, investigators propose to collect and store blood samples for all participants for future analyses.

Eligibility criteria:
inclusion criteria: * patients will be included if they meet the following criteria: * 18 and 90 years of age * transthyretin amyloid cardiomyopathy (attrwt or attrm) confirmed by genetic testing and/or presence of transthyretin precursor protein confirmed on immunohistochemical analysis, and/or scintigraphy * history of heart failure (nyha i, ii, or iii) * agreeable to treatment with tafamidis exclusion criteria: * patients will be excluded if any one of the following criteria are not met: * heart failure not due to transthyretin amyloid cardiomyopathy * new york heart association (nyha) class iv heart failure * presence of light-chain amyloidosis (serum or urine) * implanted cardiac device at baseline * treatment with attr stabilizer or gene silencer within the past 6 months